The adequacy of informed consent forms in genetic research in Oman: a pilot study

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms.     

Coding and consent: moral challenges of the database project in Iceland

A major moral problem in relation to the deCODE genetics database project in Iceland is that the heavy emphasis placed on technical security of healthcare information has precluded discussion about the issue of consent for participation in the database. On the other hand, critics who have emphasised the issue of consent have most often demanded that informed consent for participation in research be obtained. While I think that individual consent is of major significance, I argue that this demand for informed consent is neither suitable nor desirable in this case. I distinguish between three aspects of the database and show that different types of consent are appropriate for each. In particular, I describe the idea of a written authorisation based on general information about the database as an alternative to informed consent and presumed consent in database research.     

DNA sampling and informed consent.

Standard consent forms for blood and tissue sampling are inadequate for DNA sampling. However, creating new and separate forms for each type of activity associated with DNA analysis (banking, linkage analysis and genetic diagnosis) tends to dissociate the participant from what is essentially a medical continuum. Furthermore, DNA sampling involves the sharing of samples and data among centres. To ensure patient control throughout this multifaceted process, we have developed an integrated approach to obtaining consent for DNA sampling at each level of participation. Movement from one level to another is reflected in the choices offered to participants. This inclusive approach is based on the underlying principle of informed consent, namely the respect for individuality, confidentiality and freedom of choice. This approach should help practitioners of medical genetics recognize the medical context of DNA sampling.     

Informed consent and ethical re-use of African genomic data

Rapid advances in human genomic research are increasing the availability of genomic data for secondary analysis. Particularly in the case of vulnerable African populations, ethics and informed consent processes need to be transparent-both to ensure participant protection, as well as to share skills and to evolve best practice for informed consent from a shared knowledge base. An open dialogue between all stakeholders can facilitate this.     

知情同意：定义、模式和挑战

从知情同意产生和发展的历史、知情同意的含义和模式方面来说明产生于一定历史背景下的知情同意,在临床和研究领域,以及生物信息库的建设中,具有一定的局限性,也面临着挑战。面对这样的挑战,不应该拘泥于对知情同意概念本身如何准确表述、模式如何创新,而更应该从知情同意所要达到的目的——保护患者、受试者和样本提供者的权益来考虑。     

A lethal phenotype associated with tissue plasminogen deficiency in humans

The role of plasminogen in preventing thrombosis requires activation by tissue plasminogen activator (t-PA) encoded by PLAT. While case–control associations have been pursued for common variants in PLAT, no disease-causing mutations have been reported. We describe a consanguineous family with two children who died shortly after birth due to complications related to severe hydranencephaly and diaphragmatic hernia. A combined exome/autozygome analysis was carried out with informed consent. We identified a homozygous null mutation in PLAT that abrogated t-PA level in patient cells. This is the first reported human knockout mutation of PLAT. The apparent association with hydranencephaly, diaphragmatic hernia and postnatal lethality requires further validation.     

Informed Consent and Genetic Information

In the last 25 years writing in bioethics, particularly in medical ethics, has generally claimed that action is ethically acceptable only if it receives informed consent from those affected. However, informed consent provides only limited justification, and may provide even less as new information technologies are used to store and handle personal data, including personal genetic data. The central philosophical weakness of relying on informed consent procedures for ethical justification is that consent is a propositional attitude, so referentially opaque: consent is given to specific propositions describing limited aspects of a situation, and does not transfer even to closely related propositions. Assembling genetic data in databases creates additional difficulties for ethical justification. This is not because genetic information is intrinsically exceptional, but because the merger of genetic and information technologies make it possible to assemble massive quantities of complex information that defeat individuals' best efforts to grasp what is at stake, or to give or withhold informed consent. The future agenda for bioethics will need to take account of both these limitations of appeals to informed consent.     

Best Practice Guidelines on Informed Consent for Weight Loss Surgery Patients

Objective: To provide evidence‐based guidelines on informed consent and the education that underlies it for legally competent, severely obese weight loss surgery (WLS) patients. Research Methods and Procedures: We conducted a systematic review of the scientific literature published on MEDLINE between 1984 and 2004. Three articles focused on informed consent for WLS; none was based on empirical studies. We summarized each paper and assigned evidence categories according to a grading system derived from established evidence‐based models. We also relied on informed consent and educational materials from six WLS programs in Massachusetts. All evidence is Category D. Recommendations were based on a review of the available literature, informed consent materials from WLS programs, and expert opinion. Results: This Task Group found that the informed consent process contributes to long‐term outcome in multiple ways but is governed by limited legal requirements. We focused our report on the legal and ethical issues related to informed consent, i.e., disclosure vs. comprehension. Recommendations centered on the importance of assessing patient comprehension of informed consent materials, the content of those materials, and the use of active teaching/learning techniques to promote understanding. Discussion: Although demonstrated comprehension is not a legal requirement for informed consent in Massachusetts or other states, the members of this Task Group found that the best interests of WLS patients, providers, and facilities are served when clinicians engage patients in active learning and collaborative decision making.     

Pharmacogenetics: the bioethical problem of DNA investment banking

Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development--protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or 'work', the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context.     

Ethical obligation and legal requirements: On informed consent practices in Bangladesh

Informed consent to medical intervention is fundamental in both ethics and law. But in practice it is often not taken seriously in developing countries. This paper provides an appraisal of informed consent practices in Bangladesh. Following a review of the ethical and legal principles of informed consent, it assesses the degree to which doctors adhere to it in Bangladesh. Based on findings of non-compliance, it then investigates the reasons for such non-compliance through an appraisal of informed consent practices in Bangladesh and provides recommendations aimed at improving such practices. The significance of this paper lies in unveiling the interdependence between the ethical and legal traits of informed consent and their ramifications on strengthening the patient-oriented approach of duty to care.     

An Australian Based Study on the Readability of HIV/AIDS and Type 2 Diabetes Clinical Trial Informed Consent Documents

The aims of this study were to measure the readability of Australian based informed consent documents and determine whether informed consent readability guidelines have been established by Australian human research ethics committees (HRECs). A total of 20 informed consent documents, 10 HIV/AIDS and 10 type 2 diabetes, were measured for readability using the Simple Measure of Gobbledygook (SMOG) and Gunning Fog Index (Fog). Published guidelines and policy statements of the two local HREC who approved the 20 clinical trials under study where examined to identify whether they had any formal policies/guidelines on the readability of informed consent documents. The two HRECs were contacted via e-mail to also determine whether they utilised any informal readability standards or “rules of thumb” that may not have been mentioned in the published documents. The HIV/AIDS and type 2 diabetes informed consent documents were, on average, written at a grade 13 reading level. Formal readability standards had not been established by the two local HRECs, however, they did verify the use of informal rules for assessing readability of informed consent documents. Based on Australian literacy data, the majority of informed consent documents were written well beyond the reading ability of many Australians. Unreadable informed consent documents may result in patients rejecting trial participation altogether or conversely may result in their participating in a trial with inadequate consent. Therefore, a step toward reducing the complexity of informed consent documents may be to implement objective readability assessments into the human research ethics application and review process.     

Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: A case study

To date, more than seven families have been reported who carry a mutation in the X-linked creatine-transporter (CrT) gene. The resulting lack of creatine in the brain is associated with mental retardation, severe expressive language disorder, mild epilepsy, and a complete absence of Cr in the brain (measured using MRS). Conversely, these patients had no observable cardiac or musculo-skeletal deficits. In this case study, a 22-year-old patient underwent surgical repair for scoliosis. Proton MRS of this patient's brain demonstrated the near-absence of creatine and phosphocreatine within the cerebral white and deep gray matter structures. Cerebral atrophy was noted with serial MRI examinations. Subsequent genetic and metabolic analysis showed some biochemical anomalies consistent with a CrT deficiency. The mutation in this patient was identified as a deletion at phenylalanine 107 (delF107). Control muscle biopsies were obtained from archived samples, which had been taken with informed consent during routine muscle biopsies for diagnostic purposes. We determined that the total Cr concentration in the skeletal muscle biopsy was 39.3 +/- 2.94 mmol/kg wet wt., which is not significantly different from non-CrT controls, n = 3 (43.3 +/- 3.57 mmol/kg wet wt.). We conclude that the brain appears to lack the ability to transport creatine when there is a mutation in the CrT gene. However, the muscle utilizes another mechanism for maintaining normal creatine levels. Identifying this alternative creatine-transport mechanism may be useful in treating the neurologic and cognitive impairments of patients with creatine-transporter deficiency.     

Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal

Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent.     

Medical experimentation, informed consent and using people

In this paper we argue that the standard focus on problems of informed consent in debates about the ethics of human experimentation is inadequate because it fails to capture a more fundamental way in which such experiments may be wrong. Taking clinical trials as our case in point, we suggest that it is the moral offence of using people as mere means which better characterizes what is wrong with violations of personal autonomy in certain kinds of clinical trials. This account also helps bring out another important way in which the autonomy of the participants in clinical trials my be violated, even in cases where they have given informed consent to their involvement. Where relevant information about the trial is framed in such a way as to induce a patient's participation by appeal to their nonrational preferences, this is also a violation of their autonomy, and one which is distinct from a failure of informed consent. The underlying wrongness of both kinds of violations, we argue, is plausibly captured by the moral offence of using people as mere means.     

On Taylor's justification of medical informed consent

In contemporary Western biomedical ethics, informed consent practices are commonly justified in terms of the intrinsic value of patient autonomy. James Stacey Taylor maintains that this conception of the moral grounding of medical informed consent is mistaken. On the basis of his reasoning to that effect, Taylor argues that medical informed consent is justified by the instrumental value of personal autonomy. In this article, I examine whether Taylor's justification of medical informed consent is plausible.     

The ethics of learning from patients

Is it ethical for medicine to use patients as learning tools for medical students if these patients have not been given a chance to provide truly informed consent? Dr. Caroline Shooner raises this question in the following article, which claimed second prize in CMAJ''s 1996 Logie Medical Ethics Essay Contest. She considers the case of a patient whose trust was shaken when a medical student performed a chest-tube insertion. Shooner concludes that psychologic harm could have been avoided had the patient''s right to informed consent been respected. She also argues that few patients will turn down a chance to help students learn if the request is made properly and openly.     

Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital.

To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability.     

Consent for participating in clinical trials ‐ Is it really informed?

The article explores the challenges of ensuring voluntary and informed consent which is obtained from potential research subjects in the north‐eastern part of Romania. This study is one of the first empirical papers of this nature in Romania. The study used a quantitative survey design using the adapted Quality of Informed Consent (QuIC) questionnaire. The target population consisted of 100 adult persons who voluntarily enrolled in clinical trials. The informed consent form must contain details regarding the potential risks and benefits, the aim of the clinical trial, study design, confidentiality, insurance and contact details in case of additional questions. Our study confirmed that although all required information was included in the ICF, few clinical trial participants truly understood it. We also found that the most important predictive factor for a good subjective and objective understanding of the clinical trial was the level of education. Our study suggests that researchers should consider putting more effort in order to help clinical trials participants achieve a better understanding of the informed consent. In this way they will ensure that participants’ decision‐making is meaningful and that their interests are protected.     

进行性骨化性纤维増殖不良症临床及基因突变分析

目的：研究一例具有超经典型临床特征的FOP患者,并对其ACVR1/ALK2基因进行分析。方法：根据患者的大踇趾畸形和进行性异位骨化等表现进行临床诊断,确诊为FOP。经患者及家属同意,采集患者、父母外周血,提取DNA,通过PCR扩增并直接测序测定ACVR1基因全部外显子序列,以此来确定突变位点。结果：患者具有超经典型FOP的临床表现：先天性大踇趾畸形,先天性双手拇指、食指远端关节僵直和进行性异位骨化,父母无FOP的相关临床表现。基因测序分析示该患者在ACVR1第七外显子发现存在c.1067G〉A（p.G356D）杂合错义突变,而其父母无此杂合突变。结论：该患者在ACVR1的c.1067G〉A（p.G356D）发生杂合错义突变,这有助于我们更好地理解认识中国FOP患者的临床表现和发病机制。